The aging ACI/Seg versus Copenhagen male rat as a model system for the study of prostatic carcinogenesis

In untreated male ACI/Seg rats, the incidence of microscopic cancer of the ventral prostate is zero below the age of 16 months but increases to greater than 80% by 36 months of age, while the incidence of grossly manifest cancer of the ventral prostate is zero before the age of 20 months and increases to 16% by 36 months of age. In contrast, in untreated male Copenhagen rats, the incidence of microscopic prostatic cancer is only 10%, and the incidence of grossly manifest prostatic cancer is less than 1% even at 36 months of age. Analysis of the relationship between ACI/Seg host age and the incidence of microscopic versus grossly manifest prostatic cancer suggests that microscopic prostatic cancer is the result of a multistep process and that additional events are required for the progression of microscopic to grossly manifest prostatic cancer. Comparison of the serum levels of sex steroid hormones between aging male ACI/Seg and Copenhagen rats reveals substantial differences, suggesting that alterations in the serum testosterone:estrogen ratio may be one of the factors involved in prostatic carcinogenesis in the ACI/Seg rat. Chronic elevation of serum testosterone levels in these male ACI/Seg rats by means of exogenous testosterone treatment alone, however, does not induce the precocious development of microscopic prostatic cancer in young (i.e., less than 1 year of age) animals, suggesting that other factors, in addition to alterations in serum levels of testosterone, are required for prostatic carcinogenesis in the male ACI/Seg rat.